Minimum Residual Disease (MRD) is currently identified using pathologic examination, cytogenetics, fluorescence activated cell sorting, and polymerase chain reaction (PCR). Pathologic examination, which assesses cancer cell morphology, is the standard method, but the detection limit is only 10/-1 to 10/-2. PCR has a detection limit of approximately 10/-5, but suffers, but suffers from lack of quantitation and spurious results during the amplification process. Fluorescence in situ hybridization (FISH) overcomes problems of sensitivity and specificity of current methods. Development of improved FISH probes, such as dual fusion probes for detecting chromosomes translocations, and automated slide scanning instrumentation, which permits analysis of up to 1,000 cells per second, make FISH an ideal method for detecting rare cancer cells in MRD and monitoring the efficacy of treatment. Using automated slide scanning instrumentation and novel dual fusion FISH probes, this Phase I SBIR aims to develop an automated system for performing interphase FISH analysis. Phase I research will use the t(14:18)(q32;q21) translocation, which characterizes approximately 60% of B-cell Non-Hodgkin's Lymphoma, as a model system. Phase I research will compare the sensitivity, reliability and throughput of the proposed automated method with conventional manual analysis.
By providing an automated, rapid, quantitative system for detecting rare cancer cells, the proposed system will facilitate early diagnosis of cancer and detection of Minimal Residual Disease, and permit monitoring of the efficacy of cancer treatments.
